Clinical Guidance

SPTLC1-related hereditary sensory neuropathy (HSN) is usually first noticed when painless injuries appear. Onset ranges from the teens to the sixth decade. Later, positive sensory phenomena occur (numbness, paresthesia, burning, and shooting pains). Shooting pains may be a distinctive but variable feature of SPTLC1-related HSN. If the sensory loss is unheeded, chronic ulcerations of the extremities may lead to osteomyelitis and require amputations. Neuropathic joints are common. Weakness commences in the distal lower limbs, followed by the distal upper limbs and in severe cases, proximal upper- and lower-limb girdle muscles. Distal muscle weakness and wasting are present in all advanced cases. The weakness of ankle flexors produces a floppy, flipper-like foot rather than pes cavus.

Source: GeneReviews — "SPTLC1-Related Hereditary Sensory Neuropathy"

Penetrance

Variable penetrance has been observed .

Source: GeneReviews — "SPTLC1-Related Hereditary Sensory Neuropathy"

Differential Diagnosis

Dominant forms of hereditary sensory neuropathy (HSN) are genetically heterogeneous:

• HSAN1B (OMIM 608088), a dominantly inherited sensory neuropathy without foot ulcers but with cough and gastroesophageal reflux disease, maps to chromosome 3p24-p22.

• HSAN1C (OMIM 613640) is caused by pathogenic variants in SPTLC2. The neuropathy is phenotypically similar to SPTLC1-related HSN.

• HSN1D (OMIM 613708) is caused by pathogenic variants in ATL1.

• HSN1E (hereditary sensory neuropathy with dementia and hearing loss), a late-onset mild sensory neuropathy associated with ataxia and deafness, is caused by pathogenic variants in DNMT1.

Disorders with similar phenotypes are two forms of CMT2:

Source: GeneReviews — "SPTLC1-Related Hereditary Sensory Neuropathy"

Clinical Guidance

Opiates are contraindicated as this is a chronic disorder.

Source: GeneReviews — "SPTLC1-Related Hereditary Sensory Neuropathy"

Therapies Under Investigation

found that SPTLC1 pathogenic variants associated with HSN result in decreased specificity of the active site of the enzyme, allowing alanine and glycine into the active site and producing neurotoxic sphingoid bases. The finding suggests that SPTLC1-related HSN is caused by these toxic products and opens an avenue for possible (at present, experimental) therapeutic approaches. Addition of serine to the diet of an HSN1A animal model and to 14 humans with SPTLC1-related HSN was effective in reducing plasma levels of the toxic deoxysphingolipids . Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "SPTLC1-Related Hereditary Sensory Neuropathy"